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Immunostaining of Biocytin-filled and Processed Sections for Neurochemical Markers
Published on: December 31, 2016
Local interneurons regulate synaptic strength by retrograde release of endocannabinoids
Michael Beierlein1, Wade G Regehr
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Summary
Cerebellar interneurons, like stellate cells, release endocannabinoids to modulate synapse strength. This retrograde signaling, involving cannabinoid receptor 1 (CB1R) and NMDA receptors, fine-tunes cerebellar circuit activity.
Area of Science:
- Neuroscience
- Cellular signaling
- Synaptic plasticity
Background:
- Retrograde endocannabinoid signaling modulates synaptic transmission in principal neurons.
- Its role in cerebellar local interneurons remained uncharacterized.
Purpose of the Study:
- To investigate endocannabinoid release from cerebellar inhibitory interneurons (stellate cells and basket cells).
- To determine if interneurons regulate parallel fiber synapse strength via endocannabinoids.
Main Methods:
- Electrophysiological recordings in cerebellar slices.
- Pharmacological manipulation with CB1R antagonists, BAPTA, and DAG lipase inhibitors.
- Experiments in mice lacking CB1R.
- Stimulation of parallel fibers and interneurons.
Main Results:
- Depolarization-induced suppression of excitation (DSE) and synaptically evoked suppression of excitation (SSE) were observed in stellate cells.
- These effects required postsynaptic calcium elevation and CB1R activation.
- NMDA receptors (NMDARs) were crucial for SSE in stellate cells, unlike in Purkinje cells.
- Interneuron-released endocannabinoids reduced disynaptic inhibition in Purkinje cells.
Conclusions:
- Cerebellar interneurons release endocannabinoids through NMDAR- and mGluR-dependent pathways.
- This endocannabinoid release contributes to use-dependent circuit modulation.
- Local interneurons actively participate in regulating cerebellar circuit function.
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